Influenza A virus is a pathogen that causes serious illness in humans. Strains can be classified by reference to the subtype of their hemagglutinin (HA) and neuraminidase (NA) surface proteins. There are currently sixteen known HA subtypes (H1 to H16), which are antigenically distinct from each other, and nine NA subtypes (N1 to N9). Influenza A viruses currently in circulation in the human population are either H1N1 or H3N2 strains.
Influenza pandemics arise when an influenza A virus strain emerges which is capable of human-to-human (horizontal) transmission and which has a new HA or NA subtype relative to currently circulating strains. For instance, the human population is currently immunologically naïve to H5N1 strains, which have been circulating for some years in avian populations. If a H5N1 strain becomes adapted to human-to-human transmission then it could cause a widespread outbreak of influenza infection.
Current approaches to dealing with an H5N1 outbreak include prophylactic immunization or the use of neuraminidase inhibitors such as oseltamivir (Tamiflu™) and zanamivir (Relenza™). Reference 1 reports that chimeric monoclonal antibodies, with human constant domains (κ light chain and IgG1 heavy chain) and murine variable domains, can neutralize H5N1 viral strains and are thus suitable for use in prophylaxis and therapy. Reference 2 discloses murine monoclonal antibodies prepared against avian influenza strain A/Ck/HK/Yu22/02 and proposes that they might be humanised.
Within the H5 subtype, viruses fall into different lineages, termed clades on the basis of the HA sequence. Viruses isolated in Vietnam and Indonesia in 2004 and 2005, respectively, were designated as reference strains for Clades 1 and 2 (sometimes referred to using roman numerals I and II). The antibodies of reference 1 were prepared against A/Vietnam/1203/04 and A/Hong Kong/213/03 strains, both of which are in clade 1 [3].
There is a need for further and improved materials for preventing and treating H5N1 influenza A virus infections and disease, including the various clades of H5N1.